Blood Flow, Muscle Atrophy, Muscle Weakness
Conditions
Keywords
neuromodulation, skin perfussion, muscle dysfunction
Brief summary
Post-intensive care syndrome (PICS) encompasses persistent physical, cognitive, and psychiatric symptoms following ICU discharge, commonly triggered by serious conditions such as respiratory failure, sepsis, and mechanical ventilation. PICS prevalence is reported to be as high as 84% up to 12 months in patients with at least 2 days spent in the ICU or with mechanical ventilatory support. As a consequence, many patients do not return to they former level of function for weeks, months and even years. Muscular affection manifested by muscle weakness is particularly seen and is provoked by a combination of damage to the nerves or directly the muscles fibers. This affection is referred to as CU-Acquired Weakness (ICUAW). One third of the time, lower extremities are affected, often due to prolonged immobilization or sedation. Evidence suggests that early mobilization reduces the incidence of ICUAW at discharge and improves the number of patients able of stand. However achieving this early intervention is not always feasible due to time or personnel constraints. The purpose of the study is to examine the effectiveness of lower extremity neuromodulation for prevention of muscle deconditioning in patients admitted to the ICU.
Detailed description
The purpose of the study is to examine feasibility and acceptability of lower extremity neuromodulation in patients at risk of ICUAW. This is a proof Randomized controlled trial (RCT) study for prevention. Eligible participants will be recruited from Baylor St Luke's Medical Center (Houston, Texas). Participants will be randomized to intervention group (IG) or control group (CG). The entire cohort will receive daily neuromodulation in the lower extremity (Gastrocnemius muscle, Achilles tendon) up to 1 hour. The therapy will be provided with a neuromodulation device (Tennant Biomodulator PRO®, AVAZZIA, Inc.) that works on high voltage alternative pulsed current. The device will be functional for the IG and non-functional for the CG.
Interventions
DEVICEIntervention Group
Subjects will receive a functional neuromodulation device to wear for 1 hour daily up to four weeks or until hospital discharge, whichever came first.
DEVICEControl Group
Subjects will receive a non-functional neuromodulation device to wear for 1 hour daily up to four weeks or until hospital discharge, whichever came first.
Sponsors
Avazzia, Inc
Bijan Najafi, PhD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Caregiver)
Masking description
Devices may be active or sham.
Intervention model description
Participants will be randomized to intervention (IG) or control group (CG) with ratio of 1:1. The entire cohort will receive daily neuromodulation in lower extremity (e.g. Gastronemius muscle) for up to 1 hour. The neuromodulation device will be functional for IG and non-functional for CG. Phase I will include patients admitted to the Intensive care Unit. The study duration will be 4 weeks or until hospital discharge, whichever comes first.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Any patient older than 18 years old admitted to the ICU within 2 days. * Patient can be intubated with ventilatory assistance or not.
Exclusion criteria
* Less than 48 hours of ICU stay. * Major foot problems such as active lower extremity wounds, major foot deformity (e.g., Charcot Foot), and/or previous major amputations. * Demand-type cardiac pacemaker, implanted defibrillator, or other implanted electronic devices. * Any conditions that may interfere with outcomes or increase the risk of the use neuromodulation therapy based on the judgement of clinicians.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gastrocnemius Muscle Endurance at Endpoint | Up to 4 weeks | Gastrocnemius muscle endurance was assessed by measuring sustained involuntary muscle contractions using surface electromyography (sEMG; Delsys Trigno). During a 60-minute electrical stimulation therapy session, sEMG signals were recorded from the last two minutes of the therapy to evaluate muscle activity in response to electrical stimulation. The recorded sEMG data were normalized to the average sEMG signals captured during the same interval, yielding values in normalized units (n.u.), higher values indicate higher muscle endurance. The endpoint was defined as either the last day in the hospital or the completion of week 4 of the intervention, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Gastrocnemius Muscle Thickness at 4 Weeks Compared to Baseline | Up to 4 weeks | The thickness of the medial gastrocnemius muscle was measured using a portable muscle ultrasound device (Vscan Air). Changes in gastrocnemius thickness (measured in cm) from baseline to the endpoint were calculated, and the average change was reported. The endpoint was defined as either the last day in the hospital or the completion of week 4 of the intervention, whichever occurred first |
| Percentage of Tissue Oxygen Saturation at Endpoint | up to 4 weeks | Percentage of tissue oxygen saturation was measured at endpoint (study conclusion) at three time points: before neuromodulation (minute 0), immediately after 1 hour of neuromodulation (minute 60), and 10 minutes post-neuromodulation (minute 70) at the plantar region, following the protocol described by Zurbaran-Rojas et al. (Physiological Reports, 2023, DOI: 10.14814/phy2.15636). A non-invasive near-infrared spectroscopy camera (Snapshot, Kent Imaging) will be used to obtain oxygen saturation in response to neuromodulation. The endpoint was defined as either the last day in the hospital or up to week 4 of the intervention, whichever came first. |
| Ankle Strength at 4 Weeks | up to 4 weeks | Maximum Voluntary Contraction will be assed using a dynamometer during isometric plantar flexion for 5 seconds. |
| Sural Nerve Conduction at 4 Weeks | up to 4 weeks. | Sural nerve conduction will be assessed using the DPN check device (Neurometrix Inc). |
| Sural Nerve Amplitude at 4 Weeks | up to 4 weeks. | Sural nerve amplitude will be assessed using the DPN check device (Neurometrix Inc). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Independence Activities of Daily Living (ADL) 4 Weeks After Hospital Discharge | 1 month after study termination (up to 8 weeks). | Independence activities of daily living will be measured using Katz Index Scale . The minimum score is 0, meaning patient independent, and the maximum score is 6, meaning patient very dependent. |
| Instrumental Activities of Daily Living (IADL) 4 Weeks After Hospital Discharge | 1 month after study termination (up to 8 weeks). | Independence in Instrumental activities of daily living will be measured Lawton Brody Scale . The minimum score is 0, meaning low function-dependent, and the maximum score is 8, meaning high function independent. |
| Individuals Mobility and Participation in Various Life Spaces or Environments | 1 month after study termination (up to 8 weeks). | Individuals functional mobility and extent of community engagement will be measured with the UAB life space questionnaire. The minimum score is 0, totally bed-bound, and the maximum score is 120, meaning traveling everyday out of town without assistance. |
| Deep Vein Thrombosis Events at 4 Weeks | 4 weeks | The incidence of deep vein thrombosis was documented from electronic health records at week 4 following the initiation of the intervention. |
| Anxiety Level 4 Weeks After Hospital Discharge | 1 month after study termination (up to 8 weeks). | Anxiety levels will be measured using the Beck anxiety inventory validated questionnaire. The minimum score is 0, meaning low anxiety, and the maximum score is 63 , meaning potential concerning levels of anxiety. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention Subjects will receive a functional neuromodulation device to wear for 1 hour daily up to four weeks or until hospital discharge, whichever came first.
Intervention Group: Subjects will receive a functional neuromodulation device to wear for 1 hour daily up to four weeks or until hospital discharge, whichever came first. | 12 |
| Control Subjects will receive a non-functional neuromodulation device to wear for 1 hour daily up to four weeks or until hospital discharge, whichever came first.
Control Group: Subjects will receive a non-functional neuromodulation device to wear for 1 hour daily up to four weeks or until hospital discharge, whichever came first. | 13 |
| Total | 25 |
Baseline characteristics
| Characteristic | Intervention | Control | Total |
|---|---|---|---|
| Age, Continuous | 55.9 years STANDARD_DEVIATION 11.12 | 59.4 years STANDARD_DEVIATION 9.5 | 57.7 years STANDARD_DEVIATION 10.4 |
| Body Mass Index | 26.6 kg/m^2 STANDARD_DEVIATION 3.7 | 23.8 kg/m^2 STANDARD_DEVIATION 5.3 | 25.1 kg/m^2 STANDARD_DEVIATION 4.82 |
| Diabetes | 2 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 11 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Former Smoker | 8 Participants | 4 Participants | 12 Participants |
| High Blood Pressure | 9 Participants | 8 Participants | 17 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 11 Participants | 20 Participants |
| Region of Enrollment United States | 12 participants | 13 participants | 25 participants |
| Sex: Female, Male Female | 9 Participants | 7 Participants | 16 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 13 |
| other Total, other adverse events | 0 / 12 | 0 / 13 |
| serious Total, serious adverse events | 0 / 12 | 0 / 13 |
Outcome results
Primary
Gastrocnemius Muscle Endurance at Endpoint
Gastrocnemius muscle endurance was assessed by measuring sustained involuntary muscle contractions using surface electromyography (sEMG; Delsys Trigno). During a 60-minute electrical stimulation therapy session, sEMG signals were recorded from the last two minutes of the therapy to evaluate muscle activity in response to electrical stimulation. The recorded sEMG data were normalized to the average sEMG signals captured during the same interval, yielding values in normalized units (n.u.), higher values indicate higher muscle endurance. The endpoint was defined as either the last day in the hospital or the completion of week 4 of the intervention, whichever occurred first.
Time frame: Up to 4 weeks
Population: Lung transplant recipients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Gastrocnemius Muscle Endurance at Endpoint | 180 n.u. | Standard Deviation 12.6 |
| Control Group | Gastrocnemius Muscle Endurance at Endpoint | 178 n.u. | Standard Deviation 14.6 |
Secondary
Ankle Strength at 4 Weeks
Maximum Voluntary Contraction will be assed using a dynamometer during isometric plantar flexion for 5 seconds.
Time frame: up to 4 weeks
Population: This secondary outcome was not collected for all participants due to time constraints or participants' inability to complete the test.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Ankle Strength at 4 Weeks | 2.28 kg | Standard Deviation 0.69 |
| Control Group | Ankle Strength at 4 Weeks | 2.15 kg | Standard Deviation 0.94 |
Secondary
Change in Gastrocnemius Muscle Thickness at 4 Weeks Compared to Baseline
The thickness of the medial gastrocnemius muscle was measured using a portable muscle ultrasound device (Vscan Air). Changes in gastrocnemius thickness (measured in cm) from baseline to the endpoint were calculated, and the average change was reported. The endpoint was defined as either the last day in the hospital or the completion of week 4 of the intervention, whichever occurred first
Time frame: Up to 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Change in Gastrocnemius Muscle Thickness at 4 Weeks Compared to Baseline | -0.12 centimeters | Standard Deviation 0.1 |
| Control Group | Change in Gastrocnemius Muscle Thickness at 4 Weeks Compared to Baseline | -0.17 centimeters | Standard Deviation 0.14 |
Secondary
Percentage of Tissue Oxygen Saturation at Endpoint
Percentage of tissue oxygen saturation was measured at endpoint (study conclusion) at three time points: before neuromodulation (minute 0), immediately after 1 hour of neuromodulation (minute 60), and 10 minutes post-neuromodulation (minute 70) at the plantar region, following the protocol described by Zurbaran-Rojas et al. (Physiological Reports, 2023, DOI: 10.14814/phy2.15636). A non-invasive near-infrared spectroscopy camera (Snapshot, Kent Imaging) will be used to obtain oxygen saturation in response to neuromodulation. The endpoint was defined as either the last day in the hospital or up to week 4 of the intervention, whichever came first.
Time frame: up to 4 weeks
Population: This secondary outcome for one of the subjects in the intervention group was not collected due to time constraints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention Group | Percentage of Tissue Oxygen Saturation at Endpoint | Plantar Sat02 at 0 minutes | 60.2 Percentage of tissue oxygen saturation | Standard Deviation 7.9 |
| Intervention Group | Percentage of Tissue Oxygen Saturation at Endpoint | Plantar Sat02 at 60 minutes | 58 Percentage of tissue oxygen saturation | Standard Deviation 6.7 |
| Intervention Group | Percentage of Tissue Oxygen Saturation at Endpoint | Plantar Sat02 at 70 minutes | 59 Percentage of tissue oxygen saturation | Standard Deviation 6.1 |
| Control Group | Percentage of Tissue Oxygen Saturation at Endpoint | Plantar Sat02 at 0 minutes | 64.1 Percentage of tissue oxygen saturation | Standard Deviation 8.3 |
| Control Group | Percentage of Tissue Oxygen Saturation at Endpoint | Plantar Sat02 at 60 minutes | 64.1 Percentage of tissue oxygen saturation | Standard Deviation 9 |
| Control Group | Percentage of Tissue Oxygen Saturation at Endpoint | Plantar Sat02 at 70 minutes | 63.8 Percentage of tissue oxygen saturation | Standard Deviation 7.9 |
Secondary
Sural Nerve Amplitude at 4 Weeks
Sural nerve amplitude will be assessed using the DPN check device (Neurometrix Inc).
Time frame: up to 4 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Sural Nerve Amplitude at 4 Weeks | 10 microvolts (µV). | Standard Deviation 5.3 |
| Control Group | Sural Nerve Amplitude at 4 Weeks | 6.9 microvolts (µV). | Standard Deviation 5.3 |
Secondary
Sural Nerve Conduction at 4 Weeks
Sural nerve conduction will be assessed using the DPN check device (Neurometrix Inc).
Time frame: up to 4 weeks.
Population: This secondary outcome was not collected for all participants due to time constraints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Sural Nerve Conduction at 4 Weeks | 50.5 m/s | Standard Deviation 6.3 |
| Control Group | Sural Nerve Conduction at 4 Weeks | 47.15 m/s | Standard Deviation 8.2 |
Other Pre-specified
Anxiety Level 4 Weeks After Hospital Discharge
Anxiety levels will be measured using the Beck anxiety inventory validated questionnaire. The minimum score is 0, meaning low anxiety, and the maximum score is 63 , meaning potential concerning levels of anxiety.
Time frame: 1 month after study termination (up to 8 weeks).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intervention Group | Anxiety Level 4 Weeks After Hospital Discharge | 4.0 score on a scale |
| Control Group | Anxiety Level 4 Weeks After Hospital Discharge | 5.5 score on a scale |
Other Pre-specified
Deep Vein Thrombosis Events at 4 Weeks
The incidence of deep vein thrombosis was documented from electronic health records at week 4 following the initiation of the intervention.
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Group | Deep Vein Thrombosis Events at 4 Weeks | 0 Participants |
| Control Group | Deep Vein Thrombosis Events at 4 Weeks | 0 Participants |
Other Pre-specified
Independence Activities of Daily Living (ADL) 4 Weeks After Hospital Discharge
Independence activities of daily living will be measured using Katz Index Scale . The minimum score is 0, meaning patient independent, and the maximum score is 6, meaning patient very dependent.
Time frame: 1 month after study termination (up to 8 weeks).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intervention Group | Independence Activities of Daily Living (ADL) 4 Weeks After Hospital Discharge | 6.0 score on a scale |
| Control Group | Independence Activities of Daily Living (ADL) 4 Weeks After Hospital Discharge | 5.0 score on a scale |
Other Pre-specified
Individuals Mobility and Participation in Various Life Spaces or Environments
Individuals functional mobility and extent of community engagement will be measured with the UAB life space questionnaire. The minimum score is 0, totally bed-bound, and the maximum score is 120, meaning traveling everyday out of town without assistance.
Time frame: 1 month after study termination (up to 8 weeks).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intervention Group | Individuals Mobility and Participation in Various Life Spaces or Environments | 40.8 score on a scale |
| Control Group | Individuals Mobility and Participation in Various Life Spaces or Environments | 21.0 score on a scale |
Other Pre-specified
Instrumental Activities of Daily Living (IADL) 4 Weeks After Hospital Discharge
Independence in Instrumental activities of daily living will be measured Lawton Brody Scale . The minimum score is 0, meaning low function-dependent, and the maximum score is 8, meaning high function independent.
Time frame: 1 month after study termination (up to 8 weeks).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intervention Group | Instrumental Activities of Daily Living (IADL) 4 Weeks After Hospital Discharge | 5.5 score on a scale |
| Control Group | Instrumental Activities of Daily Living (IADL) 4 Weeks After Hospital Discharge | 2.0 score on a scale |